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Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF-κB Signaling Pathway.
Oxid Med Cell Longev. 2018; 2018:3509091.OM

Abstract

The Toll-like receptor-4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway is vital in the pathogenesis of hepatic ischemia/reperfusion (HIR) injury. Dipeptidyl peptidase-4 (DPP4) inhibitors exert protective effects on IR injury of the kidney, heart, and lung; however, their effect on the liver is still unknown. Thus, the purpose of this study was to examine whether pretreatment with vildagliptin (Vilda), a DPP4 inhibitor, produces hepatic protection against IR injury and to investigate its influence on TLR4/NF-κB signaling in a rat model. Thirty male Wistar rats were divided into 3 groups: the sham group: subjected to a sham operation and received normal saline; the HIR group: subjected to HIR and received normal saline; and the Vilda + HIR group: subjected to HIR with pretreatment of 10 mg/kg/day Vilda for 10 days intraperitoneally. Hepatic ischemia lasted for 45 minutes followed by 3-hour reperfusion; then blood and liver samples were collected for biochemical and histopathological examination. The HIR group produced a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA), nitric oxide (NO), and tumor necrosis factor alpha (TNF-α) levels and a significant reduction in the hepatic catalase level in comparison to the sham group. Moreover, a significant upregulation of gene and protein expressions of TLR4, NF-κB, and high-mobility group box-1 (HMGB1) along with caspase-3 protein expression was observed in the HIR group when compared with the sham group. Histopathological examination of the liver from the HIR group showed necrosis, sinusoidal congestion, hemorrhage, and hepatocyte degeneration. Administration of Vilda ameliorated the biochemical and histopathological changes caused by HIR. Vildagliptin showed for the first time a hepatoprotective effect in HIR injury through downregulation of TLR4/NF-κB/HMGB1 and caspase-3 hepatic expressions.

Authors+Show Affiliations

Emergency Hospital, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.Chemistry Department, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30405876

Citation

Sherif, Iman O., and Nora H. Al-Shaalan. "Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury Via the TLR4/NF-κB Signaling Pathway." Oxidative Medicine and Cellular Longevity, vol. 2018, 2018, p. 3509091.
Sherif IO, Al-Shaalan NH. Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF-κB Signaling Pathway. Oxid Med Cell Longev. 2018;2018:3509091.
Sherif, I. O., & Al-Shaalan, N. H. (2018). Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF-κB Signaling Pathway. Oxidative Medicine and Cellular Longevity, 2018, 3509091. https://doi.org/10.1155/2018/3509091
Sherif IO, Al-Shaalan NH. Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury Via the TLR4/NF-κB Signaling Pathway. Oxid Med Cell Longev. 2018;2018:3509091. PubMed PMID: 30405876.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF-κB Signaling Pathway. AU - Sherif,Iman O, AU - Al-Shaalan,Nora H, Y1 - 2018/10/14/ PY - 2018/06/20/received PY - 2018/09/13/revised PY - 2018/09/16/accepted PY - 2018/11/9/entrez PY - 2018/11/9/pubmed PY - 2018/11/27/medline SP - 3509091 EP - 3509091 JF - Oxidative medicine and cellular longevity JO - Oxid Med Cell Longev VL - 2018 N2 - The Toll-like receptor-4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway is vital in the pathogenesis of hepatic ischemia/reperfusion (HIR) injury. Dipeptidyl peptidase-4 (DPP4) inhibitors exert protective effects on IR injury of the kidney, heart, and lung; however, their effect on the liver is still unknown. Thus, the purpose of this study was to examine whether pretreatment with vildagliptin (Vilda), a DPP4 inhibitor, produces hepatic protection against IR injury and to investigate its influence on TLR4/NF-κB signaling in a rat model. Thirty male Wistar rats were divided into 3 groups: the sham group: subjected to a sham operation and received normal saline; the HIR group: subjected to HIR and received normal saline; and the Vilda + HIR group: subjected to HIR with pretreatment of 10 mg/kg/day Vilda for 10 days intraperitoneally. Hepatic ischemia lasted for 45 minutes followed by 3-hour reperfusion; then blood and liver samples were collected for biochemical and histopathological examination. The HIR group produced a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA), nitric oxide (NO), and tumor necrosis factor alpha (TNF-α) levels and a significant reduction in the hepatic catalase level in comparison to the sham group. Moreover, a significant upregulation of gene and protein expressions of TLR4, NF-κB, and high-mobility group box-1 (HMGB1) along with caspase-3 protein expression was observed in the HIR group when compared with the sham group. Histopathological examination of the liver from the HIR group showed necrosis, sinusoidal congestion, hemorrhage, and hepatocyte degeneration. Administration of Vilda ameliorated the biochemical and histopathological changes caused by HIR. Vildagliptin showed for the first time a hepatoprotective effect in HIR injury through downregulation of TLR4/NF-κB/HMGB1 and caspase-3 hepatic expressions. SN - 1942-0994 UR - https://www.unboundmedicine.com/medline/citation/30405876/Vildagliptin_Attenuates_Hepatic_Ischemia/Reperfusion_Injury_via_the_TLR4/NF_κB_Signaling_Pathway_ L2 - https://doi.org/10.1155/2018/3509091 DB - PRIME DP - Unbound Medicine ER -